Objectives: To determine the differences in a proliferation-inducing ligand (APRIL) between seropositive and seronegative rheumatoid arthritis (RA) patients and further investigate the possible pathogenesis of the two subtypes of RA.

Results: The mean serum APRIL level of seropositive RA patients was significantly higher than that of seronegative patients (26.1 +/- 31.2 vs. 8.0 +/- 10.2 ng/mL, p = 0.03). The level of APRIL in the SF of seropositive RA patients was comparable to that of seronegative patients [47.9 +/- 54.4 vs. 32.82 (6.52-59.12) ng/mL, p > 0.05]. The SF APRIL level of RA patients was higher than that of patients with other inflammatory arthritis. Dramatically increased infiltration of APRIL-positive cells in the RA synovium was observed compared with the OA group (seropositive RA vs. OA, p < 0.001; seronegative RA vs. OA, p = 0.001). The infiltration of both plasma cells and macrophages was more in seropositive RA than in OA (p = 0.013 and p = 0.003, respectively).

Conclusions: The serum APRIL levels of seropositive RA patients are significantly higher than those of seronegative RA patients. APRIL may participate in the formation of seropositive RA.